Changes In Immunological Markers Research Articles

Assessment of immune status markers during occupational lead exposure

The immune system is sensitive to the effects of environmental factors, and according to numerous studies, lead has an immunotoxic effect. At the same time, there is evidence of the multidirectional nature of the impact of lead on the immune system, determined by the degree of exposure to this heavy metal, which makes it current to study changes in immunological markers in workers of a modern lead recycling plant, taking into account levels and complexity of exposure. In the era of personalized medicine, monitoring the potential influence of occupational factors exposure on the immune system can facilitate a personalized approach to the prevention of work-related health conditions. The aim of the study: to evaluate changes in immune status markers among employees of lead recycling plant. The main group – 62 men working at a lead recycling plant, the control group – 47 men not exposed to occupational factors. Laboratory examination included a determination of the lead blood level, a clinical blood test, the serum levels of IL- 1â, IL- 10, IL- 8, MCP-1, C3 and C4 complement components, IgA, IgM, IgG. In the main group, compared to the control group, a higher number of neutrophils, lymphocytes, monocytes, higher levels of IL-8, C3 and C4 components of the complement system, and lower levels of IgM were detected. In the main group, the following changes in markers were significantly more often detected in comparison with reference values: an increase in the C3 component of complement (51.6% in the main group compared to 12.5% in the control group), decreased IgG (24.2% compared to 6.2%) and increased IgA (22.6% compared to 6.2%). Associations were identified between the lead blood level and the number of lymphocytes, the level of IgG, between work experience in contact with lead and the level of MCP-1 and C3 complement components. The results of the studies revealed the presence of changes in the immune status markers of workers at a lead recycling plant, which demonstrate a proinflammatory effect of lead and an influence on the humoral immune status. The identified changes in immunological parameters may underlie the mechanisms of formation of pathological conditions associated with lead exposure, which determines the relevance of continuing research to assess dynamic changes in immunological parameters and develop a system for monitoring the immune status of workers exposed to lead and its compounds to optimize preventive measures.

Improved prediction of prognosis and therapy response for lung adenocarcinoma after identification of DNA-directed RNA polymerase-associated lncRNAs.

DNA-directed RNA polymerase (DDRP) related genes and long non-coding RNAs (lncRNAs) play an important role in the development of lung adenocarcinoma (LUAD), the leading cause of cancer-related death worldwide. Therefore, we aimed to construct a DDRP-associated lncRNA model to predict the prognosis of LUAD and to evaluate its sensitivity to immunotherapy and chemotherapy. To construct a predictive signature, we used univariate and multivariate Cox regression analyses, as well as the least absolute shrinkage and selection operator regression analysis. The prognostic model was verified by applying the ROC curve analysis, Kaplan-Meier analysis, GO/KEGG analysis, and a predictive nomogram. Eventually, immunotherapy and drug susceptibility were examined and stemness indices were analyzed. 24 DDRP-associated lncRNAs were found as independent prognosis factors, which may be further developed as potential therapeutic vaccines for LUAD. The area under the ROC curve and the conformance index showed that the constructed model can predict the prognosis of LUAD patients. The predicted incidences of overall survival showed perfect conformance. And there were significant changes in immunological markers between the two risk subgroups in the model. Finally, an analysis of 50% maximum inhibitory concentration between the two risk subgroups showed that the high-risk subgroup was more sensitive to certain chemotherapy drugs. We constructed a model that accurately predicts the outcomes of LUAD based on 24 DDRP-related lncRNAs and provided promising treatment options for the future.

The toll of opioid dependence: A research report on the possible role of Toll-like receptor-4 and related immune markers in opioid dependence.

The opioid receptors in the central nervous system and immune system contribute to its reinforcing effect. Xenobiotics-associated molecular pattern of opioids interacts with Toll-like receptor-4 (TLR-4) on the glial cell surface and increases dopaminergic activity in the nucleus accumbens in preclinical studies. We wanted to examine whether treatment with buprenorphine-naloxone (BNX) might be associated with changes in immunological markers in individuals with opioid dependence (OD). We recruited 30 individuals with OD on buprenorphine and 30 age- and sex-matched healthy controls (HCs). We measured the neutrophil (N), lymphocyte (L), CD-4, and CD-8 T-cell count and estimated plasma TLR-4 level in the HC group once. We measured the immunological markers, craving, pain, and perceived stress in the OD group at the treatment initiation (baseline) and after 4 weeks (±2 weeks) of treatment with BNX. The mean severity score on the OD questionnaire was 72.8 (SD 5.4). At baseline, OD had a higher N: L ratio and lower lymphocyte percentage than HC. Plasma TLR-4 concentration increased significantly after 1 month of treatment (t = -3.09, P = 0.004). Craving, pain, and perceived stress correlated with absolute neutrophil count, N: L ratio, and CD-8 T-cell count, although lost significance after corrections for multiple comparisons. The increase in TLR-4 after treatment with BNX may indicate the rescue from nonprescription opioid-induced immunosuppression or the introduction of a novel xenobiotics-associated molecular pattern of BNX.

Identification and validation of a new pyroptosis-associated lncRNA signature to predict survival outcomes, immunological responses and drug sensitivity in patients with gastric cancer.

Gastric cancer (GC) ranks fifth in prevalence among carcinomas worldwide. Both pyroptosis and long noncoding RNAs (lncRNAs) play crucial roles in the occurrence and development of gastric cancer. Therefore, we aimed to construct a pyroptosis-associated lncRNA model to predict the outcomes of patients with gastric cancer. Pyroptosis-associated lncRNAs were identified through co-expression analysis. Univariate and multivariate Cox regression analyses were performed using the least absolute shrinkage and selection operator (LASSO). Prognostic values were tested through principal component analysis, a predictive nomogram, functional analysis and Kaplan‒Meier analysis. Finally, immunotherapy and drug susceptibility predictions and hub lncRNA validation were performed. Using the risk model, GC individuals were classified into two groups: low-risk and high-risk groups. The prognostic signature could distinguish the different risk groups based on principal component analysis. The area under the curve and the conformance index suggested that this risk model was capable of correctly predicting GC patient outcomes. The predicted incidences of the one-, three-, and five-year overall survivals exhibited perfect conformance. Distinct changes in immunological markers were noted between the two risk groups. Finally, greater levels of appropriate chemotherapies were required in the high-risk group. AC005332.1, AC009812.4 and AP000695.1 levels were significantly increased in gastric tumor tissue compared with normal tissue. We created a predictive model based on 10 pyroptosis-associated lncRNAs that could accurately predict the outcomes of GC patients and provide a promising treatment option in the future.

Changes in Expression of DNA-Methyltransferase and Cannabinoid Receptor mRNAs in Blood Lymphocytes After Acute Cannabis Smoking.

BackgroundCannabis use is a component risk factor for the manifestation of schizophrenia. The biological effects of cannabis include effects on epigenetic systems, immunological parameters, in addition to changes in cannabinoid receptors 1 and 2, that may be associated with this risk. However, there has been limited study of the effects of smoked cannabis on these biological effects in human peripheral blood cells. We analyzed the effects of two concentrations of tetrahydrocannabinol (THC) vs. placebo in lymphocytes of a subset of participants who enrolled in a double-blind study of the effects of cannabis on driving performance (outcome not the focus of this study).MethodsTwenty four participants who regularly use cannabis participated in an experiment in which they smoked cannabis cigarettes (5.9 or 13.4% THC) or placebo (0.02%) ad libitum. Blood samples were drawn at baseline and several times after smoking. Lymphocytes were separated and stored at –80°C for further analysis. Samples were analyzed for mRNA content for cannabinoid receptors 1 (CB1) and 2 (CB2), methylation and demethylating enzymes (DNMT, TET), glucocorticoid receptor (NRC3) and immunological markers (IL1B, TNFα) by qPCR using TaqMan probes. The results were correlated with THC whole blood levels during the course of the day, as well as THCCOOH baseline levels. Statistical analyses used analysis of variance and covariance and t-tests, or non-parametric equivalents for those values which were not normally distributed.ResultsThere were no differences in background baseline characteristics of the participants except that the higher concentration THC group was older than the low concentration and placebo groups, and the low concentration THC group had higher baseline CB2 mRNA levels. Both the 5.9 and 13.4% THC groups showed increased THC blood levels that then decreased toward baseline within the first hour. However, there were no significant differences between THC blood levels between the 5.9 and 13.4% groups at any time point. At the 4-h time point after drug administration the 13.4% THC group had higher CB2 (P = 0.021) and DNMT3A (P = 0.027) mRNA levels than the placebo group. DNMT1 mRNA levels showed a trend in the same direction (P = 0.056). The higher 13.4% THC group had significantly increased CB2 mRNA levels than the 5.9% concentration group at several post drug administration time points and showed trends for difference in effects for between 5.9 and 13.4% THC groups for other mRNAs. TET3 mRNA levels were higher in the 13.4% THC group at 55 min post-cannabis ingestion. When the high and lower concentration THC groups were combined, none of the differences in mRNA levels from placebo remained statistically significant. Changes in THC blood levels were not related to changes in mRNA levels.ConclusionOver the time course of this study, CB2 mRNA increased in blood lymphocytes in the high concentration THC group but were not accompanied by changes in immunological markers. The changes in DNMT and TET mRNAs suggest potential epigenetic effects of THC in human lymphocytes. Increases in DNMT methylating enzymes have been linked to some of the pathophysiological processes in schizophrenia and, therefore, should be further explored in a larger sample population, as one of the potential mechanisms linking cannabis use as a trigger for schizophrenia in vulnerable individuals. Since the two THC groups did not differ in post-smoking blood THC concentrations, the relationship between lymphocytic changes and the THC content of the cigarettes remains to be determined.

Single center, open label dose escalating trial evaluating once weekly oral ixazomib in ART-suppressed, HIV positive adults and effects on HIV reservoir size in vivo.

BackgroundAchieving a functional or sterilizing cure for HIV will require identification of therapeutic interventions that reduce HIV reservoir size in infected individuals. Proteasome inhibitors, such as ixazomib, impact multiple aspects of HIV biology including latency, transcription initiation, viral replication, and infected cell killing through the HIV protease – Casp8p41 pathway, resulting in latency reversal and reduced measures of HIV reservoir size ex vivo.MethodsWe conducted a phase 1b/2a dose escalating, open label trial of weekly oral ixazomib for 24 weeks in antiretroviral (ART)-suppressed, HIV positive adults (NCT02946047). The study was conducted from March 2017 to August 2019 at two tertiary referral centers in the United States. The primary outcomes were safety and tolerability of oral ixazomib. Secondary outcomes included changes in immunologic markers and estimates of HIV reservoir size after ixazomib treatment.FindingsSixteen participants completed the study. Ixazomib up to 4mg weekly was safe and well-tolerated, yielding no treatment-emergent events above grade 1. In exploratory analyses, ixazomib treatment was associated with detectable viremia that was below the lower limit of quantification (LLQ) in 9 participants, and viremia that was above LLQ in 4 of 16 participants. While treatment was associated with reduced CD4 counts [baseline 783 cells/ mm3 vs. week-24 724 cells/ mm3 p=0.003], there were no changes in markers of cellular activation, exhaustion or inflammation. Total HIV DNA and proviral sequencing were not altered by ixazomib treatment. Intact proviral DNA assay (IPDA) identified intact proviruses in 14 patients pre-treatment, and in 10/14 of those subjects post treatment values were reduced (P=0.068), allowing a calculated intact proviral half life of 0.6 years (95% CI 0.3, 2.5), compared to 7.1 years (95% CI 3.9, 18, p=0.004) in historical controls. Differentiation Quantitative Viral Outgrowth Assays (dQVOA) identified measurable proviruses in 15 subjects pre-treatment; post-treatment values were numerically reduced in 9, but overall differences were not significantly different.InterpretationOur study successfully met its primary endpoint of demonstrating the safety of ixazomib for 24 weeks in HIV infected persons. Exploratory analyses suggest that the effects observed ex vivo of latency reversal and reductions in HIV reservoir size, also occur in vivo. Future controlled studies of ixazomib are warranted.FundingThis study was funded by Millennium Pharmaceuticals Inc..; the Mayo Clinic Foundation; the National Institutes of Health, including the National Institute of Allergy and Infectious Diseases, Division of AIDS, the National Heart, Lung and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Neurological Disorders and Stroke, and the National Institute on Drug Abuse. Mayo Clinic also acknowledges generous funding support from Mr. Joseph T. and Mrs. Michele P. Betten.

Diversity of Microbial Signatures in Asthmatic Airways.

Asthma is a chronic inflammatory disease affecting the respiratory system. The global incidence of asthma is rising. Clinical and experimental models of asthma clearly indicate that the disease is multifactorial in nature with a wide array of factors contributing to progression and exacerbation, including interactions between immunological markers and the microbial community populating the respiratory tract. In particular, strict hygiene compliance during the early years of life and early exposure to antibiotics are linked to alterations in the biological environment within the airways and to changes in immunological markers, leading to allergies, such as asthma. With the gap in current research knowledge on the various non-bacterial microbial communities in the asthmatic airways, this review summarizes current methods used to assess microbial diversity as well as evidence for the link between microbial alterations and asthma, including changes in the bacterial microbiome, often characterized by the outgrowth of certain bacterial phyla such as proteobacteria and Firmicutes, in addition to disrupted mycobiome, virome, and parasitome. The current review emphasizes the dynamic, context-dependent changes in the microbiome in asthma and the importance of broad-scope analyses, covering a wide range of taxa. In conclusion, the interaction between the resident microbiota and the immune system is essential and significant in modulating the inflammatory responses; however, further investigations are needed to improve our understanding of the risk factors that disrupt the diversity of the microbiome in the different body systems.

Core Needle Biopsy of Breast Cancer Tumors Increases Distant Metastases in a Mouse Model

INTRODUCTION: Incisional biopsies, including the diagnostic core needle biopsy (CNB), routinely performed before surgical excision of breast cancer tumors are hypothesized to increase the risk of metastatic disease. In this study, we experimentally determined whether CNB of breast cancer tumors results in increased distant metastases and examine important resultant changes in the primary tumor and tumor microenvironment associated with this outcome. METHOD: To evaluate the effect of CNB on metastasis development, we implanted murine mammary 4T1 tumor cells in BALB/c mice and performed CNB on palpable tumors in half the mice. Subsequently, emulating the human scenario, all mice underwent complete tumor excision and were allowed to recover, with attendant metastasis development. Tumor growth, lung metastasis, circulating tumor cell (CTC) levels, variation in gene expression, composition of the tumor microenvironment, and changes in immunologic markers were compared in biopsied and non-biopsied mice. RESULTS: Mice with biopsied tumors developed significantly more lung metastases compared to non-biopsied mice. Tumors from biopsied mice contained a higher frequency of myeloid-derived suppressor cells (MDSCs) accompanied by reduced CD4+ T cells, CD8+ T cells, and macrophages, suggesting biopsy-mediated development of an increasingly immunosuppressive tumor microenvironment. We also observed a CNB-dependent up-regulation in the expression of SOX4, Ezh2, and other key epithelial-mesenchymal transition (EMT) genes, as well as increased CTC levels among the biopsy group. CONCLUSION: CNB creates an immunosuppressive tumor microenvironment, increases EMT, and facilitates release of CTCs, all of which likely contribute to the observed increase in development of distant metastases.

Effects of cigarette smoking on circulating leukocytes and plasma cytokines in monozygotic twins.

Despite the well-documented role of cigarette smoke in the development of chronic obstructive pulmonary disease (COPD), lung cancer and cardiovascular disease, biomarkers for screening or monitoring disease progression and outcome remain elusive, particularly for COPD and lung cancer. Inflammatory cells and mediators are likely to be involved in the disease processes, but their importance is still poorly understood. The purpose of this study was to investigate early changes in immunological markers associated with smoking in healthy monozygotic twins without a detectable disease discordant for smoking, thereby minimising data variability due to genetic background. Twenty-two monozygotic twin pairs, aged 31.5±6.3 years, entered the study. One of each twin pair was a smoker and the other a non-smoker. None of the subjects reported any diseases or clinically defined respiratory symptoms or airflow limitation. Each subject donated blood samples for determination of total leukocytes and subpopulations, lymphocyte subpopulation plus pro-inflammatory mediators (interleukin-8, tumour necrosis factor-α, soluble tumour necrosis factor-α receptors and C-reactive protein). We observed a significant increase in the number of circulating leukocytes and neutrophils in smokers compared to non-smokers. Smokers also had significantly higher numbers of B cells and CD4+ T cells, plus an increased CD4/CD8 ratio. The numbers of NK cells were statistically significant lower in smokers compared to non-smokers. While the prognostic significance of these changes is uncertain, results suggest that smoking is associated with immune changes, independent of genetic background and environmental conditions.

Safety and Tolerability of Lactobacillus reuteri DSM 17938 and Effects on Biomarkers in Healthy Adults: Results from a Randomized Masked Trial

BackgroundThere are few carefully-designed studies investigating the safety of individual probiotics approved under Investigational New Drug policies.ObjectivesThe primary aim of this prospective, double-blind placebo-controlled trial was to investigate if daily treatment of adults with Lactobacillus reuteri DSM 17938 (LR) for 2 months is safe and well-tolerated. Our secondary aim was to determine if LR treatment has immune effects as determined by regulatory T cell percentages, expression of toll-like receptors (TLR)-2 and −4 on circulating peripheral blood mononuclear cells (PMBCs), cytokine expression by stimulated PBMC, and intestinal inflammation as measured by fecal calprotectin.MethodsForty healthy adults were randomized to a daily dose of 5×108 CFUs of LR (n = 30) or placebo (n = 10) for 2 months. Participants completed a daily diary card and had 7 clinic visits during treatment and observation.ResultsThere were no severe adverse events (SAEs) and no significant differences in adverse events (AEs). There were no differences in PBMC subclasses, TLRs, or cytokine expression after treatment. The probiotic-treated group had a significantly higher fecal calprotectin level than the placebo group after 2 months of treatment: 50 µg/g (IQR 24–127 µg/g) vs. 17 µg/g (IQR 11–26 µg/g), p = 0.03, although values remained in the normal clinical range (0–162.9 µg/g). LR vials retained >108 CFUs viable organisms/ml.ConclusionsLR is safe and well tolerated in adults, without significant changes in immunologic markers. There was a small but significant increase in fecal calprotectin, perhaps indicating some element of immune recognition at the intestinal level.Trial RegistrationClinical Trials.gov NCT00922727

Changes in immunological markers and influx of macrophages following trans‐scleral thermotherapy of uveal melanoma

In trans-scleral thermotherapy (TSTT), heat is applied through the sclera in order to target an intraocular uveal melanoma. Previously, it had been shown that in uveal melanoma, hyperthermia and transpupillary thermotherapy influenced expression of immunologically relevant proteins, such as S100, HLA and heat-shock proteins (HSPs). We investigated whether TSTT induced similar changes. Experimental TSTT was applied on eleven uveal melanomas prior to enucleation. Each tumour sample was processed for histopathological examination; immunohistochemical analysis was performed to determine expression of S100, HLA, HSPs and macrophage markers. In TSTT-treated areas, expression of S100 and different HSPs was lost, while an upregulated expression of HSP GP96 was observed at the border of these areas. Expression levels of HLA-A and HLA-B varied between tumours and were not influenced by TSTT. The borders of the TSTT-treated areas showed high numbers of infiltrating macrophages, which were predominantly of the M2 phenotype. TSTT has an effect on immunological parameters with local loss of expression of HSPs and S100. The influx of M2 macrophages around the TSTT-treated areas indicates the presence of an innate immune reaction against the induced necrosis, suggesting that TSTT-treated tumour cells are removed by a macrophage-mediated tissue repair mechanism.

Alteraciones inmunológicas y de los valores de selectinas en pacientes hipertensos tratados según criterios actuales

Background and objective To calculate the relationsship of E and P selectins with immunological changes in essential hypertension. Patients and method We included 261 patients with essential hypertension with or without left ventricular hypertrophy (LVH), in whom selectins and specific cytokines were quantified. Results E-and P-selectins were increased in hypertension compared to controls [75(51) ng/mL versus 45(17) ng/mL, (p < 0.0001) and 47(18) ng/mL versus 38(15) ng/mL, (p = 0.049), respectively], as well as cytokine concentrations (p < 0.0001). Furthermore, selectin values were significantly correlated with changes in immunological markers. The multivariate analysis showed that IL-1ra (p < 0.0001) and P-selectin (p = 0.013) were independent factors of E-selectin values. For P-selectin, IL-1ra (p = 0.005), IL-8 (p < 0.0001) and selectin-E (p = 0.013) influenced on its concentration. Finally, selectin values were similar between patients with or without left ventricular hypertrophy. Conclusions Immunological activation influenced on selectin concentrations in cardiologic asymptomatic patients with essential hypertension. LVH did not induce significant changes.

High rate of infection and immune disorders in patients with hepatitis C virus after liver transplantation

The aim of this prospective study was to analyze the incidence of serious infections and changes in immunological markers after liver transplantation (LT) in a cohort of patients with hepatitis C virus (HCV). This study included 34 patients who had LT, 20 patients with HCV etiology (HCV group), and 14 patients with alcoholic etiology (non-HCV group). Patients with HCV were more likely to have severe infections (80%) in comparison with patients in the non-HCV group (42%) (P=0.05). The HCV group had a 3-fold greater likelihood of early severe bacterial infections than the non-HCV group. At 1 week post LT, the HCV group showed higher values of CD19+ B cells/microL than the non-HCV group (P<0.05). At weeks 4 and 12 post LT, the HCV group had lower values of CD19+ B cells/microL (P<0.05). Our data suggest that HCV recurrence after LT was associated with a high incidence of early severe infections and immunological alterations, which may be related to this increased risk.

A Blinded Randomized Controlled Trial Evaluating the Usefulness of a Novel Diet (Aminoprotect Care) in Dogs with Spontaneous Food Allergy

Aminoprotect Care (APC) is a novel diet composed of aminoacids, potato proteins and corn starch. The objectives of this study were to determine whether Maltese-Beagle atopic (MBA) dogs hypersensitive to corn exhibited clinical signs and changes in immunological markers after being fed APC. The study was designed as a blinded randomized controlled crossover experiment. Ten MBA dogs with signs of allergy within five days of ingesting corn were selected. Dogs were randomized to be fed either their maintenance diet with corn or APC for five days. After a washout of two weeks, diets were switched. Before and daily during each intervention, skin lesions were graded by an investigator while pruritus was assessed by another. Before and at the end of each intervention, the percentage of circulating CD4+CCR4+, corn-activated CD4+ T-lymphocytes and serum corn-specific IgE levels were measured and ratios of post:pre values calculated. During this trial, pruritus and skin lesions increased significantly in MBA dogs when ingesting corn while no such increase occurred when fed APC. Total, median and maximal pruritus values were significantly higher in MBA dogs ingesting corn compared to APC. There were no significant differences between interventions in the immunological parameters assessed. In summary, even though APC contains corn starch to which corn-sensitive MBA dogs often react, the ingestion of APC did not lead to significant increases in skin lesions or pruritus. Aminoprotect Care might prove valuable for management of food allergies. These experimental observations must be validated in large field studies.

Immunological markers in HIV-infected pregnant women

Objective: To examine immunological markers in HIV-infected pregnant women. Design: Women enrolled in the European Collaborative Study and the Swiss HIV Pregnancy Cohort were followed throughout pregnancy according to similar clinical and immunological protocols. Information was recorded at various times during pregnancy and, in some centres, also 6 weeks and 6 months post-partum. Method: Locally-weighted linear regression analysis was used to investigate changes in markers of cellular and humoral immune function during pregnancy and immediately post-partum, taking into account the serial measurement data structure. Women who received zidovudine during pregnancy were excluded. Results: Four hundred and thirty-eight women had two or more measurements during pregnancy or within 6 months of delivery. Twenty-four per cent (106) of the women reported injecting drugs during pregnancy. Mean CD4 and CD8 cell counts declined to a low level 6 months before delivery, increased gradually until delivery and rose sharply to a peak level 3 months post-partum. In contrast, CD4 and CD8 percentages were stable during pregnancy, and increased slightly thereafter. The same pattern was evident for transmitting women, those delivered by Cesarean section, and women who injected drugs during pregnancy, and there was no evidence for an association with immunosuppression. Total immunoglobulin (Ig) G levels declined gradually throughout pregnancy until delivery, and increased in the 6 month post-partum period. Total IgM and IgA levels remained stable throughout pregnancy. Conclusions: These findings suggest that pregnancy does not accelerate HIV progression, but in view of the intrinsic variability in serial CD4 counts, caution should be exercised when assessing changes in immunological markers in individual pregnant women.

HIV infection in women

To describe the influence of pregnancy on immunological marker paths and progression of HIV-infected women. Analysis of prospectively collected immunological and clinical data collected on 145 women reviewed at the City Hospital, Edinburgh, between 1985 and 1992 using a two-level random-effects model that allows for within- and between-patient variance. There were differences between the marker paths of women according to risk activity; women who had acquired HIV via injecting drug use (in addition to heterosexual intercourse) had a higher level of absolute CD4 cells, CD4% and total lymphocytes at seroconversion than those who had acquired HIV via heterosexual intercourse alone; however, immunological markers declined more steeply after seroconversion. There was no evidence that pregnancy, either before or after HIV seroconversion had an adverse effect on marker paths of HIV disease. There was a significant association between pregnancy after HIV seroconversion and post-pregnancy changes in immunological markers: an increase in the CD4% and a decrease in CD8%. However, causality cannot be implied as pregnancy itself may be associated with considerable lifestyle changes. During pregnancy the total white blood count rose due to an increase in the number of granulocytes, whereas the total lymphocyte numbers fell. The absolute CD4 lymphocyte subset counts fell progressively but the effect was due to the fall in the total lymphocyte counts, there being no influence of pregnancy on either CD4% or CD8%. In asymptomatic HIV infection, changes in the absolute levels of CD4 and CD8 lymphocyte counts are primarily related to changes in the other components of the white cell count because there were no changes in CD4% and CD8%. Pregnancy itself has no adverse effect on immunological markers of HIV.

The endogenous induction of tumor necrosis factor serum (TNS) for the adjuvant postoperative immunotherapy of cancer —Changes in immunological markers of the blood—

The endogenous induction of tumor necrosis factor serum (TNS) for cancer immunotherapy was undertaken in the immediate postoperative period using Lentinan as the primer and OK-432 as the inducer. The changes in several immunological markers of the blood were assayed and compared with a control group to clarify the effects of this treatment. Plasma TNF-alpha levels were elevated two to three hours after eliciting treatment. The neutrophil count was elevated on the 7th postoperative day (POD) and the natural killer (NK) cell activity was transiently suppressed on the 1st POD, but NK cells possessing a high activity (Leu7-CD16+) were preserved until the 7th POD. Helper/inducer (CD4+) and killer cells (CD8+ CD11-) tended to increase, and suppressor (CD8 bright+ CD11+) cells tended to decrease in the induction group. There was no difference in the levels of prostaglandin E2 (PGE2) between the groups, but a marked elevation of interferon-gamma was evident on the 1st POD in the induction group. This treatment may be useful as postoperative adjuvant immunotherapy for cancer due to its ability to induce cytokines and activate host immune mechanisms.